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Biomedical subjects

R Quirion

Publications and source records attributed to R Quirion.

At least 379 records · Page 21Linked to original sources
PubMed1984

Platelet 3H-imipramine binding: a state-dependent marker in depression.

Reduced density of 3H-imipramine binding sites (Bmax) to platelets has been reported in depressed patients during an episode of illness. In the present study we assessed the usefulness of decreased Bmax of platelet 3H-imipramine binding as an indicator of the depressed state. We also investigated the effect of long-term treatment with imipramine on platelet 3H-imipramine binding. A comparison of platelet 3H-imipramine binding in 10 drug-free depressed patients and 8 normal volunteers revealed significantly lower mean Bmax values in depressed patients, whereas the affinity (Kd) of 3H-imipramine binding was identical in both groups. A longitudinal study of platelet 3H-imipramine binding in 10 depressed patients during and after imipramine treatment (125-200 mg/day) revealed consistently low Bmax values despite clinically meaningful improvement. However, Bmax values increased significantly following complete remission and remained elevated even after imipramine had been discontinued for 4 weeks. These findings suggest that decrease in the sensity of platelet 3H-imipramine binding sites in depressed patients is not likely to be a direct drug effect and that normalization of this variable may follow clinical remission.

Adult↗
PubMed1984

Autoradiographic localization of angiotensin II receptors in rat brain.

The 125I-labeled agonist analog [1-sarcosine]-angiotensin II ( [Sar1]AII) bound with high specificity and affinity (Ka = 2 X 10(9) M-1) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system.

Angiotensin II↗
PubMed1984

Identification of benzomorphan-kappa opiate receptors in cerebral arteries which subserve relaxation.

Several 'so-called' kappa-opiate receptor agonists e.g., ketocyclazocine (Kc), ethylketocyclazocine (Ekc), bremazocine, MR-2034 and U-50488H, were tested on basilar and middle cerebral arteries of the dog in vitro for relaxant or contractile activities. Ekc, Kc and bremazocine were found to produce concentration-dependent reductions in basal tone and to relax cerebral arteries contracted with prostaglandin F2 alpha (PGF2 alpha). All three agonists appear to act on benzomorphan-kappa opiate receptors which subserve relaxation in cerebral blood vessels. MR-2034 and U-50488H were found to induce contraction in the cerebral arteries. These opiate agonists appear to act on phencyclidine (PCP) or sigma-opiate receptors which subserve contraction. A variety of pharmacological antagonists (phentolamine, propranolol, methysergide, atropine, diphenhydramine, cimetidine, naloxone) did not modify any of the cerebral vascular effects produced by the opiates. These results suggest: (1) specific benzomorphan-kappa opiate receptors which subserve relaxation exist in cerebral blood vessels; (2) some kappa agonists appear to produce, primarily, contraction in cerebral vessels via PCP or sigma-opiate receptors: and cerebral vascular muscle may provide a useful tool to analyse the molecular constitution of these two distinct and opposite-acting opiate receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1984

Characterization and autoradiographic distribution of the beta-adrenergic receptor in the rat lung.

An unexpected distribution of the beta-adrenergic receptor in the rat lung was revealed by an autoradiographic technique. [3H]-Dihydroalprenolol binding was stereoselective. L-propranolol was 300 times more potent than D-propranolol in competition experiments. Scatchard analysis revealed a Kd of 1.1 nM and Bmax of 14 fmol/mg wet weight. Relative potencies of beta-adrenergic ligands were: propranolol greater than alprenolol greater than timolol greater than pindolol greater than isoproterenol greater than epinephrine greater than soterenol greater than metoprolol greater than terbutaline greater than norepinephrine. The autoradiograms generated revealed a diffuse pattern with binding always associated with tissue structures. We conclude that beta-adrenergic receptors are extensively distributed in the lung, being present in large and small airways and blood vessels.

Animals↗
PubMed1984

A role for bombesin in sensory processing in the spinal cord.

Bombesin (BN)-containing neuronal processes were demonstrated in laminae I and II of the dorsal horn of the cat, rat, and mouse spinal cord by immunocytochemistry and radioimmunoassay. Dorsal rhizotomy in the cat resulted in a marked decrease in BN immunoreactivity in the dorsal horn indicating that BN is contained in primary sensory afferents. BN-binding sites were also localized in superficial laminae of the dorsal horn. The presence of both BN and BN-binding sites in the dorsal horn suggested that BN may be involved in sensory processing in the spinal cord. Consistent with this hypothesis, it was demonstrated that an injection of BN into the spinal cord caused a biting and scratching response indicative of sensory stimulation. The effect was similar to that observed after injection of substance P into the cord with the exception that the BN effect lasted about 100 times longer than that induced by substance P. Taken together, these data indicate that BN may be a neurotransmitter of primary sensory afferents to the spinal cord.

Afferent Pathways↗
PubMed1983

Autoradiographic localization of a calcium channel antagonist, [3H]nitrendipine, binding site in rat brain.

[3H]Nitrendipine, a calcium antagonist, binds in a saturable fashion (Kd = 1.4 nM, Bmax = 28 pmol/g tissue) to an apparent single class of sites in rat brain sections. Nifedipine and nitrendipine are potent displacers of [3H]nitrendipine binding while verapamil and D-600 are almost inactive. The autoradiographic distribution of [3H]nitrendipine binding shows high concentrations of sites in the hippocampus, in superficial layers of the cortex, in the external plexiform layer of the olfactory bulb and in the cerebellum. Lower levels are found in the striatum and the hypothalamus. Very low densities are observed in most of the remaining areas. The characteristic distribution of[3H]nitrendipine binding sites may help to reveal the mechanism by which calcium regulates brain functions.

Animals↗
PubMed1983

Comparative pharmacological properties and autoradiographic distribution of [3H]ethylketocyclazocine binding sites in rat and guinea pig brain.

[3H]Ethylketocyclazocine (EKC) binds to a single class of sites under various incubation conditions in both rat and guinea pig brain. Ligand selectivity patterns strongly suggest that [3H]EKC binds to kappa opiate receptors in both species and under both incubation conditions. Moreover, the autoradiographic distribution of [3H]EKC binding sites is very similar under both incubation conditions. In guinea pig brain, [3H]EKC binding sites are highly concentrated in deep layers of the cortex, caudate-putamen, and nucleus accumbens. In rat brain, kappa opiate receptors are mainly found in caudate-putamen, nucleus accumbens, amygdala, and thalamus. [3H]EKC binding sites are not concentrated in deep layers of the cortex in rat brain. Thus, the autoradiographic distribution of kappa opiate receptors is species-dependent.

Analgesics, Opioid↗
PubMed1983

Autoradiographic distribution of mu and delta opiate receptors in rat brain using highly selective ligands.

We have characterized the autoradiographic distribution of mu and delta opiate receptors in rat brain using [3H]-Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and [3H]D-Thr2, Thr6leu-enkephalin (DTLET), two highly selective ligands for mu and delta opiate receptors, respectively. Both ligands label an apparent single class of sites. Ligand selectivity shows that [3H]DAGO and [3H]DTLET are more selective ligands for their respective receptors than [3H]dihydromorphine (DHM) and [3H][D-Ala2,D-Leu5]enkephalin (DADLE). Autoradiographically, mu opiate receptors are highly discretely distributed in certain areas. High densities are found in "patches" in caudate-putamen, nucleus accumbens, cingulate cortex, habenula, various thalamic nuclei, amygdala, superior colliculus, and interpeduncular nucleus. Delta opiate receptors are mostly concentrated in the external plexiform layers of the olfactory bulb, caudate-putamen, olfactory tubercule, claustrum, and deep layers (layers V and VI) of the cortex. Since [3H]DAGO and [3H]DTLET are more selective ligands for their respective opiate receptor subtypes, they should be better ligands to characterize the fine distribution of mu and delta opiate receptors.

Animals↗
PubMed1983

Localization of opiate binding sites in kidney and adrenal gland of the rat.

[3H]ethylketocyclazocine (EKC) and [3H]etorphine bind to an apparent single class of sites in the rat kidney (kd = 7.3 and 5.2 nM; Bmax = 33.2 and 59.6 fmol/mg protein, respectively). No detectable binding was observed for [3H]dihydromorphine and [3H]D-Ala2,D-Leu5 enkephalin. Ligand selectivity pattern strongly suggests that both [3H]EKC and [3H]etorphine label a kappa opiate binding site since (-)bremazocine greater than EKC greater than etorphine greater than naloxone greater than dynorphin A much greater than beta-endorphin. In the adrenal gland, [3H]EKC also labels a single class of sites (Kd = 20.1 nM; Bmax = 74.7 fmol/mg protein) while no specific binding was seen with mu and delta ligands. Autoradiographically, [3H]EKC and [3H]etorphine binding sites are highly localized in kidney cortex compared to outer and inner medulla. Rather surprisingly, [3H]EKC binding sites in the adrenal are highly localized in the cortex with only low densities in the medulla. We are currently investigating the possible physiological roles of kappa agonists in kidney and adrenal gland functions.

Adrenal Glands↗
PubMed1983

Properties of the phencyclidine (PCP) receptors.

[3H]Phencyclidine (PCP, Angel Dust) receptors have been characterized using a rat brain binding section technique. [3H]PCP labels a single class of site in rat brain (KD = 46 nM; Bmax = 10.5 fmol/slice). Ligand selectivity pattern strongly suggests that [3H]PCP binds to sites relevant for its pharmacological actions. Chronic PCP treatment (10 mg/kg/day for 14 days) decreases the number of sites (Bmax) for [3H]PCP and [3H]spiperone binding but not for [3H]dihydromorphine. These modifications could be related to the development of tolerance and dependence to PCP. Visualization of [3H]PCP binding sites shows high densities of receptors in cortical areas and hippocampus. Lower densities are observed in caudate-putamen, nucleus accumbens, and amygdala. Negligible quantities of receptors are seen in brain stem and over white matter. The presence of specific [3H]PCP binding sites in rat brain suggests the possible existence of an endogenous ligand for this unique receptor.

Animals↗
PubMed1983

Synthesis and pharmacological characterization of (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6,7-benzomorphan (fluorophen), a ligand suitable for visualization of opiate receptors in vivo.

A fluorinated derivative of the benzomorphan opiate agonist phenazocine, (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6, 7-benzomorphan (fluorophen), was prepared by N-acylation of (+/-)-5,9 alpha-dimethyl-2'-hydroxybenzomorphan with (p-fluorophenyl)acetyl chloride, followed by diborane reduction of the resulting amide. Fluorination produces only a twofold opiate receptor affinity loss when measured either by bioassay or receptor binding (selectivity mu congruent to delta greater than kappa). Labeled with 18F, fluorophen should be sufficiently potent to be useful as an in vivo probe for visualizing opiate receptors by positron emission transaxial tomography (PETT).

Animals↗
PubMed1983

Phencyclidine ("angel dust") analogs and sigma opiate benzomorphans cause cerebral arterial spasm.

Several psychotomimetic phencyclidine (PCP) analogs--N-ethyl-l-phenylcyclohexylamine (PCE), N-[1-(2-thienyl)cyclohexyl]piperidine (TCP), N-[1-(thienyl)cyclohexyl ))pyrrolidine (THP), ketamine, and N,N-dimethyl-l-phenyl-cyclohexylamine (PCDEA)--were tested on basilar and middle cerebral arteries of the dog in vitro and found to induce contraction in these blood vessels with a maximal contractile activity (i.e., intrinsic activity) similar to that of PCP. The concentration-effect curves of these compounds were found to be parallel to the curve of PCP (P less than 0.01). The relative potency was PCE greater than TCP greater than PCP greater than THP greater than PCDEA greater than ketamine. A PCP analog with no psychotomimetic activity, 1-piperidinocyclohexanecarbonitrile (PCC), did not induce the blood vessels to contract, nor did the opiate morphine. Three psychotomimetic benzomorphans--pentazocine, cyclazocine, and N-allylnorcyclazocine--were found to: (i) also produce contraction; and (ii) have concentration--effect curves parallel to the curve of PCP, but with reduced intrinsic activities (i.e., maximal tensions were lowered) compared to PCP. A kappa opiate, ethylketocyclazocine, relaxed the blood vessels in a dose-dependent manner. This study provides direct evidence for a distinct PCP receptor on cerebral blood vessels and suggests that certain benzomorphans may produce cerebral vasospasm via PCP-receptor interactions.

Animals↗
PubMed1983

The role of vasopressin suppression in phencyclidine-induced diuresis.

Phencyclidine (PCP; 10 mg/kg, s.c.) produced a marked diuresis which occurred without significant changes in solute excretion. This diuresis occurred predominantly within 2 h of PCP injection, and was blocked by pretreatment with vasopressin. The maximum diuresis corresponded temporally to a significant fall in plasma vasopressin and rise in mean arterial pressure. Thus, PCP-induced diuresis is due, at least in part, to suppression of plasma vasopressin. This suppression is probably related to the rise in blood pressure, though direct effects of PCP on the neurohypophysis cannot be excluded.

Animals↗
PubMed1983

Characteristics and regulation of angiotensin II receptors in pituitary, circumventricular organs and kidney.

Receptors for angiotensin II (AII) have been identified and characterized in many AII-responsive tissues. Those in the adrenal zona glomerulosa and vascular smooth muscle undergo dynamic regulation which appears to be mediated by changes in circulating AII, and is followed by parallel changes in sensitivity to AII. Pituitary AII receptors are mainly located in lactotrophs and corticotrophs, where they mediate specific actions of AII upon prolactin and ACTH secretion, acting in conjunction with other hypothalamic regulators. In contrast to adrenal and vascular AII receptors, those in the anterior pituitary are not affected by changes in salt balance or AII infusion. In the brain, AII receptors were increased in the subfornical organ during dehydration, but show no significant changes in the other circumventricular organs. The increase in subfornical organ receptors resembles the up-regulation of AII sites which occurs in the adrenal cortex during sodium deficiency, and could play a role in potentiating the dipsogenic effect of AII in dehydration. In the rat kidney, AII receptors have been localized in both cortex and medulla by autoradiography with 125I-[Sar1]AII. While the renal cortical receptors appear to be localized to glomeruli, the most striking feature of these studies is the abundance of specific, high-affinity AII receptors in the renal medulla.

Adrenal Glands↗